Somatostatin was found to be a growth hormone inhibiting factor (somatotropin release inhibiting factor; SRIF) in 1973.
Somatostatin receptors were found to comprise five subtypes and named as SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5 respectively (e.g., Endocrinology, vol. 136, pp.3695-3697, 1995; Trends in Pharmacological Sciences, pp.87-94, 1997; Life Science, Vol.57, pp.1249-1265, 1995).
Somatostatin is known to inhibit production and/or secretion of various hormones, growth factors, and physiologically active substances. As the hormones inhibited by somatostatin, mentioned are growth hormone (GH), thyroid-stimulating hormones (TSH), prolactin, insulin, and glucagon. Therefore, somatostatin has various functions in endocrine systems, exocrine systems and nerve systems, and drugs targeting somatostatin are being developed (e.g., Endocrinology, vol.136, p.3695-3697, 1995; Trends in Pharmacological Sciences, pp.87-94, vol.18, 1997).
Diseases caused by somatostatin include life-style related diseases such as diabetes; central nervous system diseases, immune system diseases, and hormone-dependent tumors. Trials to develop somatostatin itself or somatostatin analogues as a drug have been conducted. For instance, octreotide known as a somatostatin receptor agonist has been marketed as a drug for treating hormone-dependent tumors.
As a compound having a somatostatin receptor binding activity, especially a selective SSTRL antagonist activity, there is known a compound represented by the formula: ##STR2##
wherein X represents O or H, H; Y represents --CH.sub.2 --, --O--, --NH-- or --S--; R.sub.1 represents H or C.sub.1-4 alkyl; R.sub.2 represents H, benzyl, etc.; R.sub.3 represents H, C.sub.1-4 alkyl, etc.; R.sub.4 represents hydrogen atom or halogen (WO97/03054).
As a compound which has a selective SSTR4 binding activity and is expected to have a glaucoma treating activity, there is known a compound represented by the formula: ##STR3##
(J. Am. Chem. Soc., vol.120, pp.1368-1373, 1998; WO97/43728).
On the other hand, the following compounds are known as amine compounds.
1) J. Med. Chem., vol.34, pp.2624-2633, 1991 describes, as a compound having a weak analgesic activity, a compound represented by the following formula: ##STR4##
2) JP-A 8(1996)-176087 describes 3-(N,N-dimethylaminomethyl)-1,2,3,4-tetrahydroquinoline as a synthetic intermediate of a compound represented by the formula: ##STR5##
wherein R.sub.1 represents arylamino such as ##STR6##
A represents a direct bond, methylene, ethylene, imino, oxy or thio; R.sub.9 represents C.sub.1-4 alkoxycarbonylamino-C.sub.1-4 alkyl, etc,; R.sub.10 represents hydrogen or C.sub.1-4 alkyl; R.sub.11 represents hydrogen or halogen; etc.; X represents carbonyl, etc.; R.sub.2 and R.sub.3 represent hydrogen, etc.; R.sub.5 represents hydroxyl, etc.; R.sub.6 represents hydrogen, etc.; R.sub.7 represents hydrogen, etc.; R.sub.8 represents aliphatic group, etc., which is described to be useful in the treatment of hypertension.
3) WO97/12860 describes, as a compound having an acyl-coenzyme A: cholesterol acyltransferase inhibiting activity and a lipid peroxidation inhibiting activity, a heterocyclic compound represented by the formula: ##STR7##
wherein at least one of R.sub.1, R.sub.2 and R.sub.5 represents alkyl or alkenyl which is substituted by hydroxy, an acidic group, alkoxycarbonyl or --NR.sub.9 R.sub.10 wherein R.sub.9 and R.sub.10 respectively represent hydrogen atom or lower alkyl, etc., and the remaining two groups independently represent hydrogen atom, lower alkyl or lower alkoxy; either of R.sub.2 and R.sub.5 represents a group represented by the formula: --NHCOR.sub.7 wherein R.sub.7 represents alkyl, etc., and the remaining groups represent hydrogen atom, lower alkyl or lower alkoxy; R.sub.6 represents alkyl, alkenyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, cycloalkylalkyl or arylalkyl; Z represents nitrogen atom substituted by R.sub.6, or a combined group forming 5-membered ring or 6-membered ring together with a carbon atom of benzene ring attached to the nitrogen atom and a carbon atom adjacent to the carbon atom, or a pharmaceutically acceptable salt thereof.
Conventional somatostatin and its analogues are all peptides. They are problematic in their oral absorbability, pharmacokinetics, etc. and are therefore unsatisfactory as medicines. It is desired to develop a compound which is different from conventional known compounds in its chemical structure, and which has a selective or nonselective affinity to somatostatin receptor subtypes, or an excellent somatostatin receptor binding inhibiting activity, and which has satisfactory properties as a medicine.